tbuckley/cabot-search huggingface dataset:
Assessment of the quality of multidisciplinary cancer conferences: A prospective observational study.
Authors: Opuruiche Ibekwe, Carmelo Gaudioso, Kristopher Attwood, Philip Whalen, Chukwumere E. Nwogu
Journal: Journal of Clinical Oncology (2022)

e13548 Background: Multidisciplinary cancer conferences (MCCs) serve as venues for input from a variety of clinicians in patient management. Research suggests that leveraging technology improves efficiency and effectiveness of MCCs. This study examined the current state of practice in three specialized MCCs before the implementation of a tumor board technology solution. Methods: A single-site prospective observational study was conducted at a comprehensive cancer center. A validated tool was adapted to evaluate the quality of information and discussion at the MCCs. Variables were scored on a 1-5 rating scale (poor to excellent). Audio recordings supplemented the observational data collection. Surveys were also administered to assess participants’ satisfaction with the process and case discussions. Endpoints of interest included time and quality of case preparation, presentation and discussion, and rate of clinical trials consideration. Descriptive statistics were used to summarize the demographic/clinical characteristics of patients and calculate overall scores for the MCC performance. Results: From September 2020 to March 2021, a total of 257 patients were presented at the three MCCs with a median age of 66 years. The distribution of clinical stages (AJCC)1-4 was 30.5%, 11.6%, 17.2% and 7.7%, respectively with 33.0% of the values missing. The overall quality of information presented, and the discussion was deemed average. However, presentation of patient views, case history and MCC chair contribution were considered poor, above average, and excellent, respectively (median scores = 1.0, 3.5 and 5.0). The median time per case presentation and discussion was 9.0 minutes. The median time per case preparation by the radiologist and pathologist was 8.6 and 12.0 minutes, respectively. Two hundred and eighty-three surveys were completed by attending physicians. 77.5% of them agreed that the case discussions were insightful and helped change their minds about the cases discussed and 91.2% were satisfied with the depth of case discussion. The rate of clinical trial consideration was 10.8%. Conclusions: These findings demonstrate various strengths and weaknesses of a conventional approach to MCCs in three disease sites – thoracic, breast and gynecology. A comparison of relevant parameters when a tumor board technology platform is utilized is ongoing. This may address some of the weaknesses identified in our study and extend the benefits of MCCs to more patients.
COVID-19 infections among minority patients with gastrointestinal malignancies in urban safety net academic medical centers.
Authors: Radhika Gali, Mariuxi Alexandra Viteri Malone, Sanjay Goel
Journal: Journal of Clinical Oncology (2022)

e15610 Background: COVID 19 infection has worse outcomes and is more severe among frail patients and with co-morbidities. Additionally, it was suggested by Mehta et al that gastrointestinal malignancies may have worse outcomes. Based off these findings, we have evaluated outcomes and potential predictors of these outcomes in patients with gastrointestinal malignancies and COVID 19 infection. Methods: We conducted a retrospective evaluation of 69 cases of patients between February 2020 to February 2021, that had both COVID 19 infection and a gastrointestinal malignancy, including: gastric, colon, pancreatic, biliary, and hepatic. We studied population general characteristics, most common tumors, oxygen requirements, management and death frequencies, at two urban safety net hospitals. Results: The median age of patients with gastrointestinal malignancies and COVID-19 infection was 68 (33 to 87), it was more frequently seen among males (N = 46, 67%); patients had on average 1-7 other comorbidities (N = 55, 80%), hypertension being the most common (N = 43, 62%). All patients in this study were minorities, the majority being Hispanics (N = 32, 46%), followed by African Americans (N = 21, 30%), the rest of patients were minorities such as Asians, Native Americans, and others (N = 16, 23%). We noted that more than half of patients were obese (N = 24, 35%), or overweight (N = 19, 28%), with a mean BMI of 26.24. Most patients were non-smokers (N = 39, 57%). The performance status among these patients was excellent in the large majority (ECOG 0-2; N = 62, 90%). The majority of malignant tumors were adenocarcinomas (N = 63, 91%); others included neuroendocrine tumors (N = 4, 6%) and gastrointestinal tumors (N = 2, 3%), the majority were advanced stage disease between stage III to stage IV disease (N = 38, 55%). The most common malignancy was colon cancer (N = 44, 64%), and also was the most reported deaths were among patients those patients with colon cancer (N = 13, 57%). Among patients that needed to be hospitalized (N = 43, 62%), needed some sort of oxygen supplementation (N = 36, 84%), a small number of patients required ICU admission (N = 8, 19%). When hospitalized, patients were mostly treated with hydroxychloroquine (N = 30, 70%) and steroids (N = 7, 16%). Inflammatory markers such as D-dimer, ferritin, C-RP were not reported in the majority of cases. Overall, the case fatality rate across all gastrointestinal malignancies was noted to be substantial (N = 22, 32%), 35% in males and 26% among females (p = 0.46). Conclusions: During the first year of the COVID-19 pandemic, patients with gastrointestinal malignancies who were infected, seemed to have a high chance to be admitted to the hospital (62%), once hospitalized the majority required some sort of oxygen supplementation (84%) and had a high case fatality rate from the COVID-19 infection (32%).
A phase Ib study of pembrolizumab following trans-arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): PETAL.
Authors: Claudia A.M. Fulgenzi, Alessio Cortellini, Antonio D'Alessio, Robert Thomas, Paul Tait, Paul J. Ross, Anna-Mary Young, Thomas Talbot, Robert Goldin, Caroline Ward, Bertram Bengsch, Rohini Sharma, David J. James Pinato
Journal: Journal of Clinical Oncology (2022)

e16195 Background: Trans-arterial chemoembolization (TACE) is the gold-standard for intermediate stage HCC. We hypothesised the ischemic and cytotoxic effect of TACE to boost anti-cancer immunity and to synergise with the anti PD-1 pembrolizumab (pembro). We designed a phase Ib study to test the safety and preliminary efficacy of pembro after TACE in intermediate HCC. Methods: PETAL study will enroll up to 32 patients with intermediate HCC to receive pembro 200 mg every 3 weeks for up to 1 year or until disease progression or unacceptable toxicity. The first safety-run-in phase includes 6 patients: if no dose limiting toxicities (DLTs) emerge over a 21-day window after first pembro, the others are enrolled in the expansion phase. Pembro is given within 30 days after 1 or 2 TACEs. The first phase includes 1 patient scoring Child-Pugh (CP)-B7 and the remaining have to be CP-A. Safety is the primary endpoint and is measured as the incidence of treatment-related adverse events (TRAEs), graded according to NCI CTCAEv4. Efficacy is the secondary endpoint and is evaluated as progression free survival (PFS) from first TACE, according to mRECIST criteria. Survival is estimated using Kaplan-Meier method. All the patients who have received at least one dose of pembro are evaluable for safety. Results: At the time of data cut-off, on the 14 th of January 2022, 14 patients had received at least one dose of pembro. The median age was 72 (IQR: 63.3-74.6), 79% were male, 71% were cirrhotic, 29% had viral hepatis and 43% ECOG PS 1. One patient had Child-Pugh (CP) class B7 and 13 had A. The median number of nodules was 1.5 (IQR:1-2.8), and 4.1 cm (IQR: 3.7-4.5) the median diameter. Overall, 5 patients received 2 TACEs and 9 had 1. Patients received a median of 4.5 cycles (IQR: 2.3-6.5) of pembro. No DLTs emerged in the first phase. Treatment-related adverse events (TRAE) of any grade (G) were reported in 86% of participants, 21% of participants experienced G3 TRAEs, and there were no G4 or G5 TRAEs. Specific skin-related toxicity was the most frequently reported (35%) TRAE. No patients had treatment-related liver toxicity. Causes of treatment discontinuation were PD (n=7), TRAEs (n=1), clinical deterioration in the CP B patient (n=1), COVID pandemic (n=2) and withdrawal of consent (n=1); at the time of data cut-off, mPFS from first TACE was 10.8 months (95%CI: 6.63-14.97). Conclusions: Adjuvant pembro following TACE is manageable and tolerable with signs of activity. These results prompt the investigation in larger trials. Clinical trial information: NCT03397654. [Table: see text]
Non-invasive cell-free DNA monitoring for predicting the response to neoadjuvant immunotherapy in locally advanced esophageal squamous cell carcinoma.
Authors: Zhen Wang, Xin Wang, Shi Xinying, Jianjun Qin, Yong Li, Yiqun Zhang, Qianhui Wan, Zhihua Pei, Dongliang Wang, Yin Li, Jie He
Journal: Journal of Clinical Oncology (2022)

e16040 Background: The combined modality therapy including neoadjuvant chemoradiotherapy has been selected as the standard care for locally advanced Esophageal squamous cell carcinoma (ESCC). However, the conclusive evidences to support the effectiveness of neoadjuvant immunotherapy for ESCC are rarely discussed. This study aims to investigate the molecular features of cell-free DNA (cfDNA) and the impact of their dynamic changes on the response to neoadjuvant immunotherapy in locally advanced ESCC patients. Methods: Twenty-four eligible locally advanced ESCC patients with received neoadjuvant immunotherapy were enrolled in this study. 7 patients achieved pathological complete regression (pCR) and the other 17 patients had non-pCR. The baseline, second and third blood samples (before neoadjuvant immunotherapy, at one month and two months after neoadjuvant immunotherapy, respectively) were collected from Cancer Institute and Hospital, Chinese Academy of Medical Sciences. Both cfDNA fragments and genomic DNA were extracted for enrichment of a customized panel covering exon regions of 599 genes. The dynamic analysis of gene alterations, which allows the monitoring of the response to neoadjuvant immunotherapy in locally advanced ESCC patients, were conducted based on multiple blood sampling strategy. Results: The most frequently mutated genes among all cases were TP53, KMT2D, CREBBP and KMT2B. MSI scores of both second and third blood samples were remarkablely higher than those in baseline blood samples (p = 0.002, 0.04). On the contrary, the TMB values and mean variant allele frequency (VAF) of second and third blood samples were significantly decreased compared with the baseline blood (TMB, p = 0.04, 0.03; mean VAF, p = 0.01, 0.02). Moreover, a decreasing trend of mean VAF was observed at the time-series blood samples from ESCC patients with pCR, while the mean VAF of ESCC patients with non-pCR declined in the blood samples from the second time point then increased in the blood samples from the thrid time point. Conclusions: The detection of dynamic changes of mean VAF could distinguish the pCR and non-pCR ESCC patients with neoadjuvant immunotherapy. These findings warrant further expanded prospective cohorts to validate.
Physician referral patterns and use of adjuvant therapy among stage IB-IIIA non-small cell lung cancer (NSCLC) patients (2010-2017).
Authors: Hrishikesh Kale, Wei-Jhih Wang, Viktor Chirikov, Anne Shah, Jon Apple
Journal: Journal of Clinical Oncology (2022)

e20509 Background: As the treatment landscape for early-stage NSCLC continues to evolve with the recent approvals of targeted and immunotherapy agents in the adjuvant setting, it is important to understand physician referral patterns and predictors of adjuvant therapy (AT). This study examined physician referral patterns at key treatment phases and assessed predictors of receiving AT in stages IB-IIIA NSCLC patients. Methods: A retrospective study using the linked SEER-Medicare database (01/01/2010-12/31/2017) included patients newly diagnosed with stages IB-IIIA NSCLC who received surgical resection. Specialties were identified by linking NSCLC claims to the AMA Physician Masterfile. AT was defined as the use of systemic chemotherapy or radiation therapy within 4 months of surgery. Multivariable logistic regression was conducted to assess predictors of receiving AT. Results: A total of 7,108 patients met the study criteria (53% IB; 9% IIA; 19% IIB; 20% IIIA). Primary care physicians (PCP) (71%), surgical oncologists (29%), and medical oncologists (36%) were the most frequently visited first specialists during pre-diagnosis, diagnosis to surgery, and post-surgery phases, respectively. The median time from diagnosis to surgery was 44 days. After surgery, 74% patients visited a medical oncologist (62% IB; 87% IIA; 83% IIB; 88% IIIA). About 41% received AT (21% IB; 64% IIA; 56% IIB; 69% IIIA). Of those, the median time from surgery to adjuvant therapy was 46 days. In the adjusted analysis, later stage at diagnosis and shorter referral time to medical oncologist had the highest odds of receiving AT (Table). Conclusions: The strongest predictors of receiving adjuvant therapy were time to medical oncologist post-surgery and stage at diagnosis. Future studies in the era of targeted therapies can use these results as a benchmark to optimize management and outcomes as well as assess changes in referral patterns in IB-IIIA NSCLC patients.[Table: see text]
Ultrasound based CEUS-Bosniak classification for cystic renal lesions: An 8-year clinical experience
Authors: E. Herms, J. Slotta-Huspenin, A. Gärtner, S. Preuss, K. Hauner, M. Heck, M. Autenrieth, T. Maurer, H. Kübler, K. Holzapfel, A. Sauter, U. Schwarz-Boeger, S. Wagenpfeil, U. Heemann, K.F. Stock
Journal: European Urology (2022)
RARE-05. Legal degree of disability in childhood-craniopharyngioma survivors during long-term follow-up – results of the HIT-ENDO study
Authors: Svenja Boekhoff, Julia Beckhaus, Maria Eveslage, Carsten Friedrich, Hermann L Müller
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Cranioparyngiomas are rare low-grade embryonic malformational tumors of the sellar/parasellar region. The prognosis after diagnosis during childhood and adolescence is influenced by endocrine and hypothalamic long-term sequelae. A legal status of the degree of disability (GdB), according to the German Social Code Book V that is worthy of support, provides financial means for psychosocial rehabilitation and participation of craniopharyngioma survivors. The aim of this study was to determine the association of clinical/psychosocial characteristics and quality of life (QoL) indicators with the resulting GdB. PATIENTS AND METHODS: HIT-Endo is a German registry study on craniopharyngioma patients aged ≤ 18 years at diagnosis and included before the year 2000. In a sample of 108 patients, the degree of disability and the association with endocrine, ophthalmological, neuropsychological and psychosocial parameters was analyzed after a mean follow-up period of 16 years (95% CI: 9.8-36.4). RESULTS: 44 patients (41%) did not receive a GdB, three patients (3%) received a GdB of 30-40, 43 patients (40%) a GdB of 50-90 and 18 patients (17%) the maximum GdB of 100. Higher GdB were associated with lower education, higher body mass index standard deviation and a higher degree of visual impairment and hypothalamic involvement of the craniopharyngeoma. Patients with a GdB of 100 reported loss in physical and cognitive function, as well as fatigue, dyspnea, and pain conditions, and limitations in social and occupational contexts. They further had a lower functional capacity (German daily life ability scale (FMH)) compared to those with a smaller GdB. CONCLUSION: The GdB is associated with psychosocial and physical impairments and reflects the long-term consequences of craniopharyngioma during childhood and adolescence. A low functional capacity (assessed by FMH) may indicate the eligibility for a high GdB in later life of craniopharyngioma survivors.
A prospective, randomized, multi-centre trial on the efficiency and effectiveness of proficiency based progression robotic surgical skills training
Authors: S. Puliatti, M. Amato, R. Farinha, A. Paludo, G. Rosiello, R. De Groote, L. Langhendries, M. Lassel, A. Mari, L. Bianchi, P. Piazza, B. Van Cleynenbreugel, E. Mazzone, K. Van Hove, S. Meganck, L. Maertens, L.P. Boret, F. Migliorini, S. Forte, B. Rocco, P. Kiely, S. Micali, A. Mottrie, A. Gallagher
Journal: European Urology (2022)
Survey of palliative care use in primary malignant bone tumors: An NCDB review.
Authors: Kevin McMahon, Vincent Eaton, Kishan Srikanth, Connor Tupper, Matthew Merwin, Matthew Morris, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2022)

e23514 Background: Palliative care has been associated with reduced patient symptom burden, improved physician satisfaction, and reduced cost of care. However, its use in primary bone tumors has not been well classified. Methods: This study retrospectively evaluated the use of palliative care in patients with primary malignant bone tumors (osteosarcoma, chondrosarcoma, Ewing sarcoma &amp; chordoma) diagnosed and recorded in the National Cancer Database (NCDB) between 2004 and 2018. Patients were identified by ICD-O-3 coding and patients with other malignancies were excluded. Cross Tabulations with Chi-square analysis was performed to evaluate frequencies of different patient and tumor characteristics. Multivariable logistic binary logistic regression was performed to evaluate relationships between patient and tumor characteristics and the use of palliative care. Results: 24,401 patients with primary malignant bone tumors were identified. Overall, only 2.52% had any form of palliative care utilization. Of those receiving palliative care, 55.5-65.1% were treated with only non-curative surgery, radiation, chemotherapy, or any combination of these modalities. Odds of palliative care were decreased for patients with chordomas, patients living more than 24 miles from the treatment facility, patients living in west-south-central or pacific states, or patients with private insurance, medicare, or unknown insurance status. Odds of palliative care were increased in patients with greater tumor diameter or unknown tumor size, tumors in the midline, increased tumor grade, stage 4 tumors, or patients living in urban areas. Conclusions: Palliative care use in patients with primary bone tumors increases with tumor stage, tumor grade, tumor size, midline tumors, or in patients living in urban areas, but overall utilization remains markedly low. Future studies should be done to investigate these patterns of care and help expand the utilization of palliative care.
Maturation of hiPSC-derived cardiomyocytes in cardiac microtissues promotes adult alternative splicing of sodium channel revealing mutation effects associated with cardiac arrhythmia
Authors: G Campostrini, D Ward-Van Oostwaard, G Kosmidis, AO Verkerk, CR Bezzina, CL Mummery, M Bellin
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Marie Skłodowska-Curie Actions - Individual Fellowship Background The cardiac sodium channel encoded by SCN5A gene undergoes fetal-to-adult isoform switch postnatally, regulated by alternative splicing. Various mutations in SCN5A associated with severe cardiac arrhythmia have been previously studied using cardiomyocytes derived from human induced pluripotent stem-cells (hiPSC-CMs), demonstrating the importance of a human cardiac cellular context for such analysis. Mutations in the adult isoform of SCN5A are however of difficult evaluation in hiPSC-CMs, because of their typical immature/fetal-like characteristics. Combining hiPSC-CMs in 3-dimensional microtissues together with hiPSC-derived cardiac fibroblasts and endothelial cells induced maturation in gene expression and functional properties, including electrophysiology. Purpose We investigated whether the maturation promoted by the microtissue system could reveal the functional phenotype of a mutation in the adult isoform of SCN5A. Methods We derived hiPSC-CMs from a cardiac arrhythmia patient carrying two compound mutations in SCN5A: p.W156X in exon 4 and p.R225W in the adult splicing variant of exon 6 (exon 6B). Using CRISPR/Cas9, we corrected exon 4 mutation to investigate specific effects of exon 6B mutation on sodium current by single-cell patch clamp. HiPSC-CMs were matured in tricell-type cardiac microtissues and analysed after dissociation. The mechanism underlying exon 6B expression was investigated by overexpressing or knocking-out the alternative splicing regulator MBNL1 in hiPSC-CMs. Results ddPCR analysis showed low expression of exon 6B-containing transcripts in hiPSC-CMs, accompanied by no effect of exon 6B mutation on the sodium current. Instead, maturing hiPSC-CMs in cardiac microtissues promoted SCN5A exon 6B expression and revealed the contribution of both SCN5A mutations to the diseased cellular electrophysiology. MBNL1 was upregulated in microtissues and indeed its overexpression was sufficient to increase exon 6B levels in hiPSC-CMs, while lack of MBNL1 prevented the switch of SCN5A splicing isoforms. Conclusions Our data demonstrate that a maturation of hiPSC-CMs is required to express the adult SCN5A isoform. This was achieved in the microtissue system via upregulation of MBNL1, and allowed to reveal SCN5A mutation contributions, by dissecting changes in ionic current that cause adult arrhythmic disease phenotypes in humans.
Correction to: COVID-19 in pediatric cancer patients is associated with treatment interruptions but not with short-term mortality: a Polish national study
Authors: Jadwiga Węcławek-Tompol, Zuzanna Zakrzewska, Olga Gryniewicz-Kwiatkowska, Filip Pierlejewski, Ewa Bień, Agnieszka Zaucha-Prażmo, Olga Zając-Spychała, Anna Szmydki-Baran, Agnieszka Mizia-Malarz, Wioletta Bal, Małgorzata Sawicka-Żukowska, Agnieszka Kruk, Tomasz Ociepa, Anna Raciborska, Agnieszka Książek, Tomasz Szczepański, Jarosław Peregud-Pogorzelski, Maryna Krawczuk-Rybak, Radosław Chaber, Michał Matysiak, Jacek Wachowiak, Ninela Irga-Jaworska, Wojciech Młynarski, Bożenna Dembowska-Bagińska, Walentyna Balwierz, Agnieszka Matkowska-Kocjan, Bernarda Kazanowska, Jan Styczyński, Marek Ussowicz
Journal: Journal of Hematology & Oncology (2022)